Treatment of myocardial dysfunction and pulmonary oedema in an infant chimpanzee

Abstract: The care of any critically ill infant requires special technical equipment for monitoring of cardiac and pulmonary functions including mechanical ventilators and blood gas analysers. The present paper describes the treatment of myocardial dysfunction and pulmonary distress, complicated by severe brain oedema in an infant chimpanzee admitted to an intensive care unit in the Department of Neonatology of the Children's Hospital of the University of Leipzig. The condition of the chimpanzee was diagnosed and monitored by standard clinical tooös including radiography, echocardiography, cerebral Doppler sonography and laboratory parameters. The chimpanzee was treated in close cooperation between veterinarians and paediatricians.     

SERCA2a in Heart Failure: Role and Therapeutic Prospects

Ca²⁺ is a key molecule controlling several cellular processes, from fertilization to cell death, in all cell types. In excitable and contracting cells, such as cardiac myocytes, Ca²⁺ controls muscle contractility. The spatial and temporal segregation of Ca²⁺ concentrations are central to maintain its concentration gradients across the cells and the cellular compartments for proper function. SERCA2a is a cornerstone molecule for maintaining a balanced concentration of Ca²⁺ during the cardiac cycle, since it controls the transport of Ca²⁺ to the sarcoplasmic reticulum (SR) during relaxation. Alterations of the activity of this pump have been widely investigated, emphasizing its central role in the control of Ca²⁺ homeostasis and consequently in the pathogenesis of the contractile defect seen with heart failure. This review focuses on the molecular characteristics of the pump, its role during the cardiac cycle and the prospects derived from the manipulation of SERCA2a for heart failure treatment.     

Capture-recapture studies using radio telemetry with premature radio-tag failure

Radio tags, because of their high detectability, are often used in capture-recapture studies. A key assumption is that radio tags do not cease functioning during the study. Radio-tag failure before the end of a study can lead to underestimates of survival rates. We develop a model to incorporate secondary radio-tag failure data. This model was applied to chinook smolts (Oncorhynchus tshawytscha) on the Columbia River, Washington. Estimates of fish survival from this model were much larger than those from the standard Cormack-Jolly-Seber analysis.     

Regulation of cardiac sarcoplasmic reticulum Ca release by luminal [Ca] and altered gating assessed with a mathematical model

Cardiac excitation-contraction coupling is initialized by the release of Ca from the sarcoplasmic reticulum (SR) in response to a sudden increase in local cytosolic [Ca] ([Ca]i) within the junctional cleft. We have tested the hypothesis that functional ryanodine receptor (RyR) regulation plays a major role in the regulation of myocyte Ca. A mathematical model with unique characteristics was used to simulate Ca homeostasis. Specifically, the model was designed to accurately represent the SR [Ca]-dependence of release from a variety of experimentally produced data sets. The simulated data for altered RyR Ca sensitivity demonstrated a regulatory feedback loop that resulted in the same release at lower [Ca]SR. This suggests that the primary role of myocyte RyR regulation may be to decrease SR [Ca] without decreasing the size of the [Ca]i transient. The model results suggest that this action moderates the increased SR [Ca] observed with adrenergic stimulation and may keep the [Ca]SR below the threshold for delayed afterdepolarizations and arrhythmia. However, increased Ca affinity of the RyR increased the probability of delayed afterdepolarizations when heart failure was simulated. We conclude that RyR regulation may play a role in preventing arrhythmias in healthy myocytes but that the same regulation may have the opposite effect in chronic heart failure.     

Direct measurement of Ca2+ concentration in the SR of living cardiac myocytes

Although abnormal sarcoplasmic reticulum (SR) Ca(2+) handling may cause heart failure, there has been no method to directly measure Ca(2+) concentration in SR ([Ca(2+)](SR)) of living cardiomyocytes. We have measured [Ca(2+)](SR) by expressing novel fluorescent Ca(2+) indicators yellow cameleon (YC) 2.1, YC3er, and YC4er in cultured neonatal rat cardiomyocytes. The distribution of YC2.1 was uniform in the cytoplasm, while that of YC3er/YC4er, containing the signal sequence which recruits them to SR, showed reticular pattern and was co-localized with SERCA2a. The treatment with caffeine reversibly decreased the emission ratio (R) in YC3er/YC4er-expressing myocytes, and the treatment with ryanodine and thapsigargin decreased R irreversibly. During the contraction-relaxation cycle, R was changed periodically in the YC2.1- and YC3er-expressing myocytes, but its direction of the change was opposite. These results suggest that YC3er/YC4er were specifically localized and functioned in SR as a [Ca(2+)](SR) indicator. This technique would be useful to understand the function of SR in failing myocardium.     

Gender differences in cardiac function during early remodeling after acute myocardial infarction in mice

There are conflicting data about gender differences in cardiac function after myocardial infarction (MI), including cardiac rupture and mortality. Using a mouse model of MI, we recently found that the cardiac rupture rate during the first week after MI was significantly lower in females than in males, suggesting that females have attenuated structural remodeling. Thus in this study, we attempted to determine whether: a) females have attenuated remodeling and faster healing during the early phase post-MI, and b) females have better cardiac function and outcome during the chronic phase compared to males. MI was induced in 12-week-old male and female C57BL/6J mice. Signs of early remodeling, including cardiac rupture, infarct expansion, inflammatory response, and collagen deposition, were studied during the first 2 weeks post-MI. Left ventricular remodeling and function were followed for 12 weeks post-MI. We found that males had a higher rate of cardiac rupture, occurring mainly at 3 to 5 days of MI and associated with a higher infarct expansion index. Neutrophil infiltration at the infarct border was more pronounced in males than females during the first days of MI, which were also characterized by increased MMP activity. However, the number of infiltrating macrophages was significantly higher in females at day 4. During the chronic phase post-MI, males had significantly poorer LV function, more prominent dilatation and significant myocyte hypertrophy compared to females. In conclusion, males have delayed myocardial healing, resulting in cardiac rupture, and the survivors have poorer cardiac function and pronounced maladaptive remodeling, whereas females show a better outcome during the development of HF.     

Lithospermic acid B isolated from Salvia miltiorrhiza ameliorates ischemia/reperfusion-induced renal injury in rats

The present study was designed to examine whether lithospermic acid B (LSB) isolated from Salvia miltiorrhiza has an ameliorative effect on renal functional parameters in association with the expression of aquaporin 2 (AQP 2) and Na,K-ATPase in the ischemia-reperfusion induced acute renal failure (ARF) rats. LSB showed strong antioxidant activity against production of reactive oxygen species (ROS), ROS-induced hemolysis, and production of lipid peroxide in a dose-dependent manner. Polyuria caused by down-regulation of renal AQP 2 in the ischemia-reperfusion induced ARF rats was partially restored by administration of LSB (40 mg/kg, i.p.), restoring expression of AQP 2, in renal inner and outer medulla. The expression of Na,K-ATPase alpha1 subunit in outer medulla of the ARF rats was also restored in the ARF rats by administration of LSB, while beta1 subunit level was not altered. The renal functional parameters including creatinine clearance, urinary sodium excretion, urinary osmolality, and solute-free reabsorption were also partially restored in ischemia-ARF rats by administration of LSB. Histological study also showed that renal damages in the ARF rats were abrogated by administration of LSB. Taken together, these data indicate that LSB ameliorates renal defects in rats with ischemia-reperfusion induced ARF, most likely via scavenging of ROS.     

The origin of sympathetic outflow in heart failure: the roles of angiotensin II and nitric oxide

The regulation of sympathetic nerve activity in chronic heart failure (CHF) has been an area of renewed investigation. Understanding the central mechanisms that are responsible for sympatho-excitation in this disease state may help in reducing the deleterious effects of chronic sympatho-excitation. This review will summarize our understanding of abnormal reflex control of the circulation in CHF. The roles of the arterial baroreflex, the chemoreflex, the cardiac sympathetic afferent reflex and the cardiopulmonary reflex are discussed. New experimental techniques that allow genetic manipulation of substances such as nitric oxide synthase in discrete areas of the brain aid in clarifying the role of NO in the modulation of sympathetic tone in the CHF state. Lastly, clinical implications of this work are discussed.     

Voriconazole Proves Effective in Long-Term Treatment of a Cerebral Cryptococcoma in a Chronic Nephropathic HIV-Negative Patient,after Fluconazole Failure

Although being a rare occurrence, brain cryptococcoma may represent an emerging issue, because of its relationship with a broadening range of risk factors, including malignancies, neutropenia, end-organ failure, bone marrow and solid-organ transplantation, and multiple underlying causes of primary-secondary immunodeficiency. A cerebral cryptococcoma in a chronic nephropathic HIV-negative subject with homocystinuria, completely cured with neurosurgery and voriconazole after fluconazole failure, is described.     

Patterns of treatment failure in salivary gland cancers

Aim

The purpose of the study was to publish our experience of salivary gland cancer treatment with large number of patients treated at a single institution.